We are investigating the pathophysiology of acute pulmonary edema with special reference to plasma colloid osmotic pressure (COP). Pulmonary edema is usually caused by alteration of either plasma colloid osmotic pressure - pulmonary microvascular hydrostatic pressure gradient, or capillary membrane permeability. The extent to which reduction in plasma colloid osmotic pressure potentiates the development of pulmonary edema is studied. The risk of pulmonary edema is assessed in a prospective, randomized clinical trial of volume resuscitation with either colloid or crystolloid infusion. Patients selected have a low plasma COP (less than 16), and an initially normal or low hydrostatic pressure (PAo less than 18 mmHg); they require a fluid challenge for hypovolemia, hypotension or a low perfusion state, and may be in shock or have a capillary-leak syndrome. The goal is to study the therapeutic implication concerning the correct choice of fluid for volume repletion in these critically ill patients. The development of pulmonary edema is serially assessed and quantitated by clincial symptoms and signs, by chest roentgenography, by the determination of plasma colloid osmotic pressure-pulmonary microvascular hydrostatic pressure gradient, and by concurrent measurement of intravascular plasma volume. Measurement of tracheal fluid protein content (as well as COP and I125 activity) identifies coincident changes in pulmonary vascular membrane permeability, so that hemodynamic and permeability pulmonary edema may be distinguished. It is hypothesized that a critical reduction in the colloid-hydrostatic pressure gradient is associated with hemodynamic pulmonary edema and that fluid repletion with colloids may decrease the incidence of pulmonary edemia in patients with a reduced plasma COP.